Relationship of Reproductive Hormones and Neuromuscular Disease of the Gastrointestinal Tract

Abstract

Functional disorders of the gastrointestinal tract comprise a common but ill-defined group of diseases; they primarily afflict women. Although predominantly involving nerve and muscle, the cellular and molecular bases of the pathogenesis of these functional disorders are unknown. Clinical studies indicate that some result from neural dysfunction within the enteric nervous system, others may be due to muscular problems, and the causes of still others remain unknown. Laboratory studies have shown that ovarian products such as progesterone, luteinizing hormone, human chorionic gonadotropin, and relaxin (but not estrogen), are neural antagonists of gastrointestinal motility. The production and secretion of these ovarian substances are controlled by gonadotropin-releasing hormone (GnRH) released from the hypothalamus; they probably act on γ-aminobutyric acid receptors and alter chloride influx into the cell. GnRH analogs are effective drugs that downmodulate the hypothalamic-pituitary-gonadal axis and inhibit the secretion of gonadal products involved in such hormone-dependent diseases as endometriosis and prostate cancer. Acting on the GnRH receptors (seven transmembrane domain receptors) on myenteric neurons, GnRH analogs are also effective neural modulators in such disorders as functional bowel disease. These analogs are a promising new group of compounds that may be used to treat difficult gastrointestinal problems.

Expression and distribution of GnRH, LH, and FSH and their receptors in gastrointestinal tract of man and rat

“…Continuous treatment with the GnRH analog leuprolide was shown to improve symptoms in patients with functional bowel disorders [30,31]. The mechanism behind is enigmatic, but may be due to down-regulation of the GnRH-R in the pituitary gland and subsequent depletion of gonadotropins and sex hormones [3], suggested to influence gastrointestinal motility [32,33]. Another plausible explanation to the leuprolide-induced effects is by activation of intestinal GnRH-R.…”

Effects of progesterone on gastric emptying and intestinal transit in male rats

“…Steroids, especially P and E, participate the regulation of gastrointestinal motility [3][4][5] and are involved in the pathogenesis of some functional disorders in the gut [6] . We reported that administration of estrogen inhibited the rat gastric emptying and intestinal transit while P enhanced the gut motility [7] .…”

Traumatic Brain Injury and the Gastrointestinal Tract: The Role of Female Sexual Hormones

“…In some studies, it has been reported that steroid hormones, especially progesterone and estrogen, have noticeable effects on the gastric motility and secretions [19] and are also involved in the pathogenesis of some functional disorders of the gut [20].…”

“…Therefore, it is rational to infer that, similar to other organs, E2 and progesterone may have protective effects in GI tract, and E2 plays a protecting role against acid-peptic duodenal injury in females [47]. Steroid hormones, in particular progesterone and estrogen, have effects on the gastric motility and secretions [19], and are also involved in the pathogenesis of some functional disorders in the gut [20]. This might provide a sensible explanation for the clinically observed gender difference in the prevalence of duodenal ulcer (Table 1 [ [48][49][50][51][52][53][54][55][56][57][58][59][60][61][62]).…”